PB1743: FACTORS AFFECTING THE MECHANISMS OF LEUKEMOGENESIS IN CHILDREN WITH ALL, RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS OF UKRAINE
Authors: Katerina Bruslova, Nataliia Tsvietkova, Liudmila Liashenko, Tatiana Pushkareva, Larysa Honchar, Sergii Iatsemyrskyi
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Descriptive and analytical studies reveal the mechanisms of the relationship between the state of hematopoiesis, bone structures and hormonal regulation in children with ALL Aims: Identify factors that influence the development and course of ALL in children Methods: We examined 109 ALL children aged 3 to 18 years. The children lived in radioactively contaminated areas of Ukraine (1998-2022). The anamnesis, clinical symptoms, bone metabolism parameters (stromal fibroblasts, amino acids in urine, alkaline phosphatase, calcium, vitamin D in the patients’ serum) were evaluated, as well as cholesterol, creatinine, serum ferritin and iron, and sideroblasts in the bone marrow. The hormonal profile included free thyroxine, pituitary thyroid-stimulating hormone, and cortisol. The radiation doses to the bone marrow in patients were 4.48±0.14 mSv. The radiation dose increased with the age of the child. The data were statistically processed (Student’s t-test, Spearman’s correlation coefficient, U-test) Results: Among those examined, 92.7% had B-ALL and 7.3% had T-ALL. Pro-B-ALL - 8.9%, comm.variant - 80.2%, pre-B-ALL - 10.9%. Oncological diseases were more often recorded in the family history of patients (22.9% vs. 8.9% of the control group) (p < 0.05). Bone injuries were more frequently recorded in children with AL (p < 0.05). At diagnosis, 71.6% of patients had normocytic anemia, the initial leukocyte count was lower in comm.- ALL (18.3 ± 3.4 G/L), higher in T-ALL (43.2 ± 4.5 G/L) and pro-B-ALL (63.6 ± 7.4) G/L). Also, in the initial period of ALL, cortisol levels were decreased in 25.7% of patients, and TSH levels were increased in 8.3% of patients.At the stages of chemotherapy (CT), children had calcium deficiency, iron overload, amino acid imbalance, catabolic processes prevailed and bone density decreased (p < 0.01). The survival rate of patients in the standard risk group was (173.6 ± 16.4) months, and in the high risk group - (50.2 ± 9.1) months. The maximum survival was observed in children with comm.- ALL under the age of 6 years. A worse prognosis was observed in patients over 12 years of age whose relatives had endocrine pathology ((56.5 ± 4.3) months). The predominance of the erythroid link in the BM on day 33 of CT contributed to a worse prognosis than the predominance of granulocyte-monocyte link of hematopoiesis at the corresponding time (rs = -0.57). The reasons for prolonging the course of CT were febrile neutropenia, septic processes, and toxic hepatitis. The longer the interval between the M protocol and the subsequent stages of treatment, the worse the prognosis of ALL (rs = -0.62). Elevated TSH levels at the onset of ALL affected the state of collagen structures and osteogenesis. Initial hypocortisolemia in children with ALL is accompanied by a decrease in stromal fibroblast function and a shorter survival (46.5 ± 3.2) months. Summary/Conclusion: The development and course of ALL is influenced by the genetic component, the state of the osteon and hematopoietic microenvironment, endocrine regulation, and environmental factors. Keywords: Acute lymphoblastic leukemia, Bone marrow stroma, Children, Radiation